A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors

Abstract

V106M may be a signature mutation in clade C patients treated with EFV and may have the potential to confer high-level multi-NNRTI resistance.

Mutation D30N Is Not Preferentially Selected by Human Immunodeficiency Virus Type 1 Subtype C in the Development of Resistance to Nelfinavir

“…Our present findings pertain to one specific PI. Wainberg and colleagues found that the V106M mutation confers cross-resistance to nonnucleoside reverse transferase inhibitors (4). This mutation appears frequently in subtype-C-infected patients treated with efavirenz and rarely in subtype-B-infected patients or in subtype-C-infected patients treated with nevirapine (4,9,20).…”

“…Wainberg and colleagues found that the V106M mutation confers cross-resistance to nonnucleoside reverse transferase inhibitors (4). This mutation appears frequently in subtype-C-infected patients treated with efavirenz and rarely in subtype-B-infected patients or in subtype-C-infected patients treated with nevirapine (4,9,20). Moreover, in vitro studies of this group showed that the final drug concentration required for the development of resistance mutations conferring nonnucleoside reverse transferase inhibitors resistance was significantly lower for subtype C than for subtype B viruses and that resistant variants were fully selected more rapidly with the subtype C isolates than with the subtype B control (15,16).…”

“…Although none of the primary mutations occur as polymorphisms in wild-type HIV-1, several secondary mutations contributing to reduced susceptibility (i.e., M36I and I93L) are found in nearly 100% of subtype C virus from drug-naive patients (5,10). Upon antiretroviral treatment, such differences in baseline polymorphisms among subtypes may result in the evolution of drug resistance along distinct mutational pathways, or in differences in the incidence of these specific pathways (1,4,9,12,16,25,28,29). These genetic differences may be clinically relevant when considering long-term treatment strategies for patients infected with different subtypes.…”

Involvement of the Genetic Diversity of HIV-1 in the Virological Treatment Failure of First Line Antiretroviral in Kinshasa

“…Some subtypes would develop resistance more frequently than subtypes A and B [9]; this could cause some natural nucleotide polymorphisms on specific codons [10] [11].…”

Résistance du VIH aux antirétroviraux

“…Des études effectuées récemment dans notre laboratoire, sur des isolats de sous-type C du VIH-1, ont montré la présence de polymorphismes naturels prédisposant à la résistance à certains INNTI ainsi qu'un profil de résistance spécifique à ce sous-type [25]. C'est le cas de la mutation Val106Met qui est sélectionnée par l'efavirenz (EFV) dans les souches de sous-type C et qui confère une résistance croisée aux trois INNTI commercialisés [26]. Une étude ougandaise plus récente (HIVNET 012) fait état d'une proportion plus importante de patientes porteuses de souches résistantes à la névirapine (NVP) chez les femmes infectées par le VIH-1 de sous-type D (36%) que chez celles infectées par le VIH-1 de sous-type A (19%) [27].…”